This project explores pharmacodynamic approaches to developing new treatments for drug dependence and reduction of HIV transmission risk behaviors, with a current focus on cocaine, marijuana, and nicotine dependence. Many subjects are at high risk for contracting and spreading HIV infection. Pharmacodynamic approaches being studied include modulation of brain neural circuits and neurotransmitter activity using transcranial magnetic stimulation (TMS), in collaboration with the Maryland Psychiatric Research Center. TMS involves projecting pulsed magnetic fields through the skull into the brain, where they alter neuronal firing and change levels of neurotransmitters. TMS is a well tolerated, non-invasive way of modulating activity in brain circuits that mediate drug craving and reward, thus offering a potential treatment for drug addiction. Pilot studies are being conducted to evaluate the safety and efficacy of either single-pulse or low-frequency repetitive TMS in users of cannabis, cocaine, and nicotine. A pilot study showed that functional magnetic resonance imaging (fMRI) could be successfully used to target TMS pulses to a desired brain region.